Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, Symbicort, Seretide
Brief summary
This study is to assess the effects with two different inhaled respiratory medications with regards to improvement of lung function, symptoms and morning activities.
Interventions
DRUGSymbicort Turbuhaler (budesonide/formoterol) 320/9 μg
DRUGSeretide Diskus (salmeterol/fluticasone) 50/500 μg
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Outpatient, female or male aged ≥40 years, diagnosis of COPD with symptoms for at least 2 years * FEV1 ≤50% of predicted normal value, pre-bronchodilator, FEV1/VC \<70% * Pre-bronchodilator
Exclusion criteria
* Current respiratory tract disorder other than COPD * History of asthma or rhinitis * Significant or unstable cardiovascular disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Expiratory Flow (PEF) 5 Minutes After Morning Dose | Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days | The change from baseline in PEF was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and all days of treatment, with baseline as covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PEF 15 Minutes After Morning Dose | Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days | The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. |
| PEF Before Evening Dose | Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days | The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. |
| Forced Expiratory Volume in 1 Second (FEV1) Before Morning Dose | Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days | The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. |
| FEV1 15 Minutes After Morning Dose | Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days | The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. |
| FEV1 Before Evening Dose | Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days | The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. |
| Change in PEF From Before Dose to 5 Minutes After Dose in the Morning | Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days | The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with pre-dose run-in/washout as covariate. |
| Change in PEF From Before Dose to 15 Minutes After Dose in the Morning | Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days | The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with mean pre-dose run-in/washout as covariate. |
| PEF Before Morning Dose | Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days | The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. |
| Change in FEV1 From Before Dose to 15 Minutes After Dose in the Morning | Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days | The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with mean pre-dose run-in/washout as covariate. |
| Change in FEV1 From Before Dose to 5 Minutes After Dose at the Clinic | Baseline (run-in, and washout) and day 1 of treatment period | The change from pre-dose was calculated using the pre-dose baseline value (run-in and washout period respectively), and pre-dose value at day 1, with pre-dose run-in/washout as covariate. |
| Change in Forced Vital Capacity (FVC) From Before Dose to5 Minutes After Dose at the Clinic | Baseline (run-in, and washout) and day 1 of treatment period | The change from pre-dose was calculated using the pre-dose baseline value (run-in and washout period respectively), and pre-dose value at day 1, with pre-dose run-in/washout as covariate. |
| Capacity of Daily Living in the Morning (CDLM) (Change From Pre to End of Treatment) | Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days | The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. Score scale 0 - 5 with 0=worst and 5 = best. |
| Difficulty in Getting Out From Bed (MASQ) (Change From Pre to End of Treatment) | Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days | The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. Score scale 0 - 5 with 0=worst and 5 = best. |
| The Clinical Chronic Obstructive Pulmonary Disease (COPD) Questionnaire (Change From Pre to End of Treatment) | Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days | The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. Score scale 0 - 6 with 0=worst and 6 = best. |
| Change in FEV1from Before Dose to 5 Minutes After Dose in the Morning | Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days | The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with mean pre-dose run-in/washout as covariate. |
Countries
Argentina, Australia, Belgium, Brazil, Denmark, Germany, India, Philippines, United Kingdom
Participant flow
Recruitment details
706 subjects were enrolled; 264 were not randomised: 190 with eligibility not fulfilled, 11 with adverse events, 4 with discontinuation criteria, 40 voluntary discontinuations, 2 lost to follow-ups, 6 non-compliance, 1 for safety reasons, 10 with other reasons not specified. 442 subjects were randomised
Participants by arm
| Arm | Count |
|---|---|
| Symbicort Turbuhaler First, Then Seretide Diskus Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg First, then Seretide Diskus (salmeterol/fluticasone) 50/500 μg | 217 |
| Seretide Diskus First, Then Symbicort Turbuhaler Seretide Diskus (salmeterol/fluticasone) 50/500 μg First, then Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg | 225 |
| Total | 442 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 2 | 2 |
| Period 1 | Development of study-specific criteria | 1 | 2 |
| Period 1 | Eligibility criteria not fulfilled | 2 | 6 |
| Period 1 | Protocol Violation | 0 | 1 |
| Period 1 | Withdrawal by Subject | 1 | 1 |
| Period 2 | Adverse Event | 5 | 7 |
| Period 2 | Discontinuation criteria | 2 | 0 |
| Period 2 | Eligibility not fulfilled | 0 | 1 |
| Period 2 | Other | 0 | 1 |
| Period 2 | Severe non-compliance | 0 | 1 |
| Period 3 | Adverse Event | 0 | 2 |
Baseline characteristics
| Characteristic | Symbicort Turbuhaler First, Then Seretide Diskus | Seretide Diskus First, Then Symbicort Turbuhaler | Total |
|---|---|---|---|
| Age Continuous | 62.9 years | 63.2 years | 63.1 years |
| Sex: Female, Male Female | 55 Participants | 71 Participants | 126 Participants |
| Sex: Female, Male Male | 162 Participants | 154 Participants | 316 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 420 | 0 / 429 |
| serious Total, serious adverse events | 3 / 420 | 1 / 429 |
Outcome results
Primary
Peak Expiratory Flow (PEF) 5 Minutes After Morning Dose
The change from baseline in PEF was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and all days of treatment, with baseline as covariate.
Time frame: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler | Peak Expiratory Flow (PEF) 5 Minutes After Morning Dose | 15.1 liters/minute | Standard Deviation 28.5 |
| Seretide Diskus | Peak Expiratory Flow (PEF) 5 Minutes After Morning Dose | 13.4 liters/minute | Standard Deviation 28.2 |
Secondary
Capacity of Daily Living in the Morning (CDLM) (Change From Pre to End of Treatment)
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. Score scale 0 - 5 with 0=worst and 5 = best.
Time frame: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler | Capacity of Daily Living in the Morning (CDLM) (Change From Pre to End of Treatment) | 0.1920 units on a scale | Standard Deviation 0.253 |
| Seretide Diskus | Capacity of Daily Living in the Morning (CDLM) (Change From Pre to End of Treatment) | 0.1240 units on a scale | Standard Deviation 0.231 |
Secondary
Change in FEV1 From Before Dose to 15 Minutes After Dose in the Morning
The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with mean pre-dose run-in/washout as covariate.
Time frame: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler | Change in FEV1 From Before Dose to 15 Minutes After Dose in the Morning | 0.0930 Liters | Standard Deviation 0.187 |
| Seretide Diskus | Change in FEV1 From Before Dose to 15 Minutes After Dose in the Morning | 0.0280 Liters | Standard Deviation 0.163 |
Secondary
Change in FEV1 From Before Dose to 5 Minutes After Dose at the Clinic
The change from pre-dose was calculated using the pre-dose baseline value (run-in and washout period respectively), and pre-dose value at day 1, with pre-dose run-in/washout as covariate.
Time frame: Baseline (run-in, and washout) and day 1 of treatment period
Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler | Change in FEV1 From Before Dose to 5 Minutes After Dose at the Clinic | 0.1120 Liters | Standard Deviation 0.195 |
| Seretide Diskus | Change in FEV1 From Before Dose to 5 Minutes After Dose at the Clinic | 0.0440 Liters | Standard Deviation 0.164 |
Secondary
Change in FEV1from Before Dose to 5 Minutes After Dose in the Morning
The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with mean pre-dose run-in/washout as covariate.
Time frame: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler | Change in FEV1from Before Dose to 5 Minutes After Dose in the Morning | 15.8 Liters | Standard Deviation 20.8 |
| Seretide Diskus | Change in FEV1from Before Dose to 5 Minutes After Dose in the Morning | 9.6 Liters | Standard Deviation 19.9 |
Secondary
Change in Forced Vital Capacity (FVC) From Before Dose to5 Minutes After Dose at the Clinic
The change from pre-dose was calculated using the pre-dose baseline value (run-in and washout period respectively), and pre-dose value at day 1, with pre-dose run-in/washout as covariate.
Time frame: Baseline (run-in, and washout) and day 1 of treatment period
Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler | Change in Forced Vital Capacity (FVC) From Before Dose to5 Minutes After Dose at the Clinic | 0.0950 Liters | Standard Deviation 0.137 |
| Seretide Diskus | Change in Forced Vital Capacity (FVC) From Before Dose to5 Minutes After Dose at the Clinic | 0.0490 Liters | Standard Deviation 0.106 |
Secondary
Change in PEF From Before Dose to 15 Minutes After Dose in the Morning
The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with mean pre-dose run-in/washout as covariate.
Time frame: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler | Change in PEF From Before Dose to 15 Minutes After Dose in the Morning | 11.6 Liters/minute | Standard Deviation 16.2 |
| Seretide Diskus | Change in PEF From Before Dose to 15 Minutes After Dose in the Morning | 6.1 Liters/minute | Standard Deviation 16.5 |
Secondary
Change in PEF From Before Dose to 5 Minutes After Dose in the Morning
The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with pre-dose run-in/washout as covariate.
Time frame: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler | Change in PEF From Before Dose to 5 Minutes After Dose in the Morning | 0.0160 Liters/minute | Standard Deviation 0.2 |
| Seretide Diskus | Change in PEF From Before Dose to 5 Minutes After Dose in the Morning | 0.0030 Liters/minute | Standard Deviation 0.299 |
Secondary
Difficulty in Getting Out From Bed (MASQ) (Change From Pre to End of Treatment)
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. Score scale 0 - 5 with 0=worst and 5 = best.
Time frame: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler | Difficulty in Getting Out From Bed (MASQ) (Change From Pre to End of Treatment) | 0.21 Units on a scale | Standard Deviation 0.64 |
| Seretide Diskus | Difficulty in Getting Out From Bed (MASQ) (Change From Pre to End of Treatment) | 0.14 Units on a scale | Standard Deviation 0.75 |
Secondary
FEV1 15 Minutes After Morning Dose
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate.
Time frame: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
Population: Includes all subjects with at least one dose of study medication and contribute sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler | FEV1 15 Minutes After Morning Dose | 0.1220 Liters | Standard Deviation 0.253 |
| Seretide Diskus | FEV1 15 Minutes After Morning Dose | 0.1030 Liters | Standard Deviation 0.372 |
Secondary
FEV1 Before Evening Dose
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate.
Time frame: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler | FEV1 Before Evening Dose | 0.1470 Liters | Standard Deviation 0.247 |
| Seretide Diskus | FEV1 Before Evening Dose | 0.1060 Liters | Standard Deviation 0.201 |
Secondary
Forced Expiratory Volume in 1 Second (FEV1) Before Morning Dose
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate.
Time frame: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
Population: Includes all subjects with at least one dose of study medication and contribute sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler | Forced Expiratory Volume in 1 Second (FEV1) Before Morning Dose | 0.0310 Liters | Standard Deviation 0.246 |
| Seretide Diskus | Forced Expiratory Volume in 1 Second (FEV1) Before Morning Dose | 0.0590 Liters | Standard Deviation 0.231 |
Secondary
PEF 15 Minutes After Morning Dose
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate.
Time frame: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler | PEF 15 Minutes After Morning Dose | 19.9 Liters/minute | Standard Deviation 30.3 |
| Seretide Diskus | PEF 15 Minutes After Morning Dose | 16.7 Liters/minute | Standard Deviation 28.5 |
Secondary
PEF Before Evening Dose
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate.
Time frame: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler | PEF Before Evening Dose | 4 Liters/minute | Standard Deviation 24.3 |
| Seretide Diskus | PEF Before Evening Dose | 1.8 Liters/minute | Standard Deviation 50 |
Secondary
PEF Before Morning Dose
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate.
Time frame: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler | PEF Before Morning Dose | 4.8 Liters/minutes | Standard Deviation 28.2 |
| Seretide Diskus | PEF Before Morning Dose | 7.9 Liters/minutes | Standard Deviation 24 |
Secondary
The Clinical Chronic Obstructive Pulmonary Disease (COPD) Questionnaire (Change From Pre to End of Treatment)
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. Score scale 0 - 6 with 0=worst and 6 = best.
Time frame: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symbicort Turbuhaler | The Clinical Chronic Obstructive Pulmonary Disease (COPD) Questionnaire (Change From Pre to End of Treatment) | 0.24 Units on a scale | Standard Deviation 0.75 |
| Seretide Diskus | The Clinical Chronic Obstructive Pulmonary Disease (COPD) Questionnaire (Change From Pre to End of Treatment) | 0.19 Units on a scale | Standard Deviation 0.73 |